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Rapid, high sensitivity, point-of-care test for cardiac troponin based on optomagnetic biosensor
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2010-04-12
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| Author: |
Dittmer, W.U.
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Evers, T.H.
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Hardeman, W.M.
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Huijnen-Keur, W.M.
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Kamps, R.
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De Kievit, P.
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Neijzen, J.H.M.
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Sijbers, M.J.J.
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Nieuwenhuis, J.H.
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Hefti, M.H.
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Dekkers, D.
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Martens, M.
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| Keywords: |
magnetic biosensor · point of care · sandwich immunoassays · troponin i (tni)
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BACKGROUND: We present a handheld integrated device based on a novel magnetic-optical technology for the sensitive detection of cardiactroponin I, a biomarker for the positive diagnosis of myocardial infarct, in a finger-prick blood sample. The test can be performed with a turn-around time of 5 minutes and can detect concentrations in the picomolar range in a sample volume of less than 25 L. METHOD: The test was completed in a compact, injection molded plasticdisposable with a 0.5 L assay chamber containing integrateddry magnetic nanoparticles and reagents. We have developed a 1-stepassay in which all reaction processes were precisely controlled bythe 3 electromagnetic coils positioned above and below the disposable. In the on-sensor assay, troponin molecules were sandwiched between capture antibodies attached to the detection surface and 500 nm superparamagnetic particles functionalized with tracer anti-troponinantibodies. Nanoparticles bound to the sensor surface were sensitively detected using the optical technique of frustrated total internalreflection (f-TIR). RESULT: A calibration function measured in 100%human plasma using our integrated test demonstrates a limit of detection (mean of blank plus 3 SD) of 0.03 ng/mL (1 pM) cTnI for a turn-around time of approximately 5 minutes. A linear regression analysis of the region 0.03-6.5 ng/mL yields a slope of 37 ± 4, intercept of 0.22±0.01 and linear correlation coefficient of R2=0.98. The measuring range could be extended substantially, to 100 ng/mL, by simultaneously imaging a second spot with lower capture antibody concentration. CONCLUSION: The combination of magnetic particles and their actuation with electromagnets permits the sensitive detection of cTnIto be performed rapidly. Because of the speed, ease-of-use and highanalytical sensitivity of the test, it is well suited for demandingpoint-of-care medical diagnostic applications.
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[PDF]
[Abstract]
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